G Piscosquito1, M M Reilly2, A Schenone3, G M Fabrizi4, T Cavallaro4, L Santoro5, F Manganelli5, G Vita6,7, A Quattrone8, L Padua9, F Gemignani10, F Visioli11,12, M Laurà2, D Calabrese1, R A C Hughes2, D Radice13, A Solari1, D Pareyson1. 1. C. Besta Neurological Institute, IRCCS Foundation, Milan, Italy. 2. MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, London, UK. 3. Department of Neurology, Ophthalmology and Genetics, University of Genoa, Genoa, Italy. 4. Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Verona, Italy. 5. Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Naples, Italy. 6. Department of Neurosciences, University of Messina, Messina, Italy. 7. Clinical Centre NEMO SUD, Fondazione Aurora Onlus, Messina, Italy. 8. Neurology Clinic, Neuroimaging Research Unit, National Research Council, Magna Graecia University, Catanzaro, Italy. 9. Department of Geriatrics, Neurosciences and Orthopaedics - Università Cattolica del Sacro Cuore, Rome, Don Carlo Gnocchi Foundation, Milan, Italy. 10. Department of Neurosciences, University of Parma, Parma, Italy. 11. Department of Pharmacological Sciences, University School of Pharmacy, Milan, Italy. 12. Department of Molecular Medicine, University of Padua, Padua, Italy. 13. Department of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
Abstract
BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease (CMT) is a very slowly progressive neuropathy which makes it difficult to detect disease progression over time and to assess intervention efficacy. Experience from completed clinical trials with ascorbic acid and natural history studies confirm difficulties in detecting such changes. Consequently, sensitive-to-change outcome measures (OMs) are urgently needed. METHODS: The relative responsiveness of clinical scales of the Italian-UK ascorbic acid trial (placebo arm) were assessed by using the standardized response mean (SRM), which is the ratio of the paired scores mean change over time to the standard deviation of the score change (0 is worst responsiveness). RESULTS: Little worsening of OM scores was found over 2 years. In detail, the primary OM of the trial, the CMT Neuropathy Score version 1 (CMTNSv1), showed low responsiveness (SRM 0.13). Some CMTNS items showed slightly greater responsiveness (CMT Examination Score 0.17; CMTNS Signs 0.19). Myometric assessments of handgrip and foot dorsiflexion strength were the most responsive (SRM -0.31 and -0.38, respectively). Amongst the other measures, the nine-hole peg test, which assesses upper limb functioning, showed the best sensitivity to change (SRM 0.28). CONCLUSIONS: Overall these OMs showed low or negligible responsiveness, confirming the need to improve current OMs and to develop novel ones for prognostic and interventional studies. However, handgrip and foot dorsiflexion myometry are worth retaining for future trials as they were the most responsive and are likely to be clinically relevant for patients.
BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease (CMT) is a very slowly progressive neuropathy which makes it difficult to detect disease progression over time and to assess intervention efficacy. Experience from completed clinical trials with ascorbic acid and natural history studies confirm difficulties in detecting such changes. Consequently, sensitive-to-change outcome measures (OMs) are urgently needed. METHODS: The relative responsiveness of clinical scales of the Italian-UK ascorbic acid trial (placebo arm) were assessed by using the standardized response mean (SRM), which is the ratio of the paired scores mean change over time to the standard deviation of the score change (0 is worst responsiveness). RESULTS: Little worsening of OM scores was found over 2 years. In detail, the primary OM of the trial, the CMT Neuropathy Score version 1 (CMTNSv1), showed low responsiveness (SRM 0.13). Some CMTNS items showed slightly greater responsiveness (CMT Examination Score 0.17; CMTNS Signs 0.19). Myometric assessments of handgrip and foot dorsiflexion strength were the most responsive (SRM -0.31 and -0.38, respectively). Amongst the other measures, the nine-hole peg test, which assesses upper limb functioning, showed the best sensitivity to change (SRM 0.28). CONCLUSIONS: Overall these OMs showed low or negligible responsiveness, confirming the need to improve current OMs and to develop novel ones for prognostic and interventional studies. However, handgrip and foot dorsiflexion myometry are worth retaining for future trials as they were the most responsive and are likely to be clinically relevant for patients.
Authors: Francis B Panosyan; Callyn A Kirk; Devon Marking; Mary M Reilly; Steven S Scherer; Michael E Shy; David N Herrmann Journal: Muscle Nerve Date: 2017-07-21 Impact factor: 3.217
Authors: Vera Fridman; Stefan Sillau; Gyula Acsadi; Chelsea Bacon; Kimberly Dooley; Joshua Burns; John Day; Shawna Feely; Richard S Finkel; Tiffany Grider; Laurie Gutmann; David N Herrmann; Callyn A Kirk; Sarrah A Knause; Matilde Laurá; Richard A Lewis; Jun Li; Thomas E Lloyd; Isabella Moroni; Francesco Muntoni; Emanuela Pagliano; Chiara Pisciotta; Giuseppe Piscosquito; Sindhu Ramchandren; Mario Saporta; Reza Sadjadi; Rosemary R Shy; Carly E Siskind; Charlotte J Sumner; David Walk; Janel Wilcox; Sabrina W Yum; Stephan Züchner; Steven S Scherer; Davide Pareyson; Mary M Reilly; Michael E Shy Journal: Neurology Date: 2020-02-11 Impact factor: 9.910
Authors: Åsa Sandelius; Henrik Zetterberg; Kaj Blennow; Rocco Adiutori; Andrea Malaspina; Matilde Laura; Mary M Reilly; Alexander M Rossor Journal: Neurology Date: 2018-01-10 Impact factor: 9.910
Authors: Menelaos Pipis; Shawna M E Feely; James M Polke; Mariola Skorupinska; Laura Perez; Rosemary R Shy; Matilde Laura; Jasper M Morrow; Isabella Moroni; Chiara Pisciotta; Franco Taroni; Dragan Vujovic; Thomas E Lloyd; Gyula Acsadi; Sabrina W Yum; Richard A Lewis; Richard S Finkel; David N Herrmann; John W Day; Jun Li; Mario Saporta; Reza Sadjadi; David Walk; Joshua Burns; Francesco Muntoni; Sindhu Ramchandren; Rita Horvath; Nicholas E Johnson; Stephan Züchner; Davide Pareyson; Steven S Scherer; Alexander M Rossor; Michael E Shy; Mary M Reilly Journal: Brain Date: 2020-12-01 Impact factor: 13.501